Chelidonine Induces Apoptosis via GADD45a-p53 Regulation in Human Pancreatic Cancer Cells

Chelidonium majus has been used as a traditional medicine in China and western countries for various diseases, including inflammation and cancer. However, the anti-cancer effect of chelidonine, a major compound of C. majus extracts, on pancreatic cancer remains poorly understood. In this study, we found that treatment with chelidonine inhibited proliferation of BxPC-3 and MIA PaCa-2 human pancreatic cancer cells. Annexin-V/propidium iodide staining assay showed that this growth inhibitory effect of chelidonine was induced through apoptosis. We found that chelidonine treatment upregulated mRNA levels and transcription factor activity in both cell lines. Increases in protein expression levels of p53, GADD45A, p21 and cleaved caspase-3 were also observed, with more distinct changes in MIA PaCa-2 cells compared to the BxPC-3 cells. These results suggest that chelidonine induces pancreatic cancer apoptosis through the p53 and GADD45A pathways. Our findings provide new insights into the use of chelidonine for the treatment of pancreatic cancer.

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Transcript profiling identifies novel key players mediating the growth inhibitory effect of NS-398 on human pancreatic cancer cells

European Journal of Pharmacology ◽

10.1016/j.ejphar.2010.10.026 ◽

2011 ◽

Vol 650 (1) ◽

pp. 170-177 ◽

Cited By ~ 18

Author(s):

Mahmoud Youns ◽

Thomas Efferth ◽

Jörg D. Hoheisel

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Inhibitory Effect ◽

Transcript Profiling ◽

Human Pancreatic Cancer ◽

Growth Inhibitory Effect ◽

Pancreatic Cancer Cells ◽

Growth Inhibitory ◽

Key Players

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Growth inhibitory effect of lithium salt of gamma linolenic acid on human pancreatic cancer cells in-vitro

Gastroenterology ◽

10.1016/0016-5085(95)26424-8 ◽

1995 ◽

Vol 108 (4) ◽

pp. A528 ◽

Cited By ~ 1

Author(s):

D. Ravichandran ◽

AC Cooper ◽

CD Johnson ◽

SJ Karran

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Lithium Salt ◽

Inhibitory Effect ◽

Human Pancreatic Cancer ◽

Gamma Linolenic Acid ◽

Growth Inhibitory Effect ◽

Pancreatic Cancer Cells ◽

Growth Inhibitory

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Effect of zeb1 and zeb2 on pancreatic fibrobast-induced epithelial-to-mesenchymal transition (EMT) in pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e21035 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e21035-e21035

Author(s):

Laura Visa ◽

Esther Samper ◽

Mariana Rickmann ◽

Antonio Postigo ◽

Esther Sanchez-Tillo ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Smooth Muscle Actin ◽

Human Pancreatic Cancer ◽

Mrna Levels ◽

Rt Pcr ◽

Epithelial Tumor ◽

Mesenchymal Transition ◽

Pancreatic Cancer Cells ◽

E Cadherin

e21035 Background: EMT renders neoplastic cancer cells the ability to migrate and to invade distant organs. The hallmark of EMT is the loss of E-cadherin, which is a prerequisite for epithelial tumor cell invasion. In pancreatic cancer, loss of tumor E-cadherin is an independent predictor of poor outcome. Aims: To analyze the effect of pancreatic fibroblasts (PF) on inducing EMT in pancreatic cancer cells and to identify the transcription factors (Snail, Slug, ZEB1, ZEB2) that mediate EMT process. Methods: Human PFs were isolated from human pancreatic specimens obtained from chronic pancreatitis and from unaffected margins of pancreatic adenocarcinoma and serous cistoadenoma. PF were cultured until complete cellular activation, as assessed by expression of α-smooth muscle actin, vimentin and fibronectin. Human pancreatic cancer cells Panc-1 were exposed to PF conditioned medium (PF-CM) and EMT analyzed by cell morphology, migration, and E-cadherin expression (quantitative RT-PCR and immunoblot). Gene expression of Snail, Slug, ZEB1, and ZEB2 was analyzed by quantitative RT-PCR, and their activity modulated by siRNA Results: Conditioned media from all types of activated PFs induced EMT changes in Panc-1 cells, as shown by 1) morphological transition from cobblestone shaped to fibroblast-like cells, 2) stimulation of cell migration, and 3) E-cadherin down–regulation; mRNA expression of Snail transiently increased at 30 min after exposure to PF returning to basal levels afterwards; mRNA levels of ZEB1 were not up-regulated upon exposure to PF-CM. However, ZEB1 protein greatly accumulated after 48h incubation with PF-CM, suggesting that PF prevent ZEB1 degradation in Panc-1 cells. Combined RNA downregulation of ZEB1 and ZEB2, but not of Snail and/or Slug, suppressed E-cadherin repression induced by PF. Conclusions: Activated PFs promote the invasive phenotype of pancreatic cancer cells through ZEB1 and ZEB2 activation.

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